RC48 Combined With Adebrelimab, Apatinib and S-1 as Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Official title

Disitamab Vedotin Combined With Adebrelimab, Apatinib and S-1 as Neoadjuvant Therapy in Locally Advanced Gastric Cancer With HER2 Overexpression: a Prospective, Phase II Study

Overview

This study is a prospective, open-label, phase II clinical trial that aims to enroll patients with locally advanced gastric adenocarcinoma who have not received any prior treatment and are candidates for surgery. The study drugs include RC48, Adebrelimab, Apatinib and S-1. The purpose is to evaluate the effectiveness and safety of the combined coordinated treatment of multi-mechanism drugs for perioperative treatment of locally advanced gastric cancer with HER2 overexpression.

Detailed description

The study plans to enroll 32 subjects. After signing the informed consent form and meeting the inclusion and exclusion criteria, patients will receive standard-dose treatment of the RC48, Adebrelimab, Apatinib and S-1 regimen for 3-4 cycles (every 3 weeks) before surgery. Apatinib will only be used for 14 days in the last cycle. Imaging studies will be conducted 3-4 weeks after the last dose to assess the efficacy of neoadjuvant therapy and the possibility of radical D2 gastrectomy. The treatment plan after curative surgery for gastric cancer will be determined by the investigators and the patients based on the pathological findings. Patients who benefit clinically after surgery may receive adjuvant therapy with RC48, Adebrelimab, Apatinib and S-1 for 4 cycles (the first treatment is expected to start around 4 weeks after surgery) or follow the standard postoperative adjuvant regimen recommended by the guidelines.

Interventions

• Drug RC48
  RC48: 2.5 mg/kg, intravenous infusion, on day 1, every 3 weeks (Q3W);
• Drug Adebrelimab
  Adebrelimab：1200 mg, intravenous infusion, on day 1, every 3 weeks (Q3W);
• Drug Apatinib
  Apatinib: 250mg, oral administration, once daily (qd), every 3 weeks (Q3W);
• Drug S-1
  S-1：For patients with a body surface area (BSA) ≤1.5m², use 50mg each time; for patients with BSA \>1.5m², use 60mg each time, oral administration, twice daily (bid), on days 1-14, every 3 weeks (Q3W);

Primary outcome measures

• Pathological Complete Response Rate (pCR) [Time frame: 4 months]

Secondary outcome measures (4)

• Major Pathological Response rate (MPR) [Time frame: 4 months]
• R0 Resection rate [Time frame: 4 months]
• Disease-Free Survival (DFS） [Time frame: 24 months]
• Overall Survival (OS) [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• 1\. Participants voluntarily join this study, are able to complete the signing of the informed consent form, and have good compliance;
• 2\. Age between 18 to 75 years old (at the time of signing the informed consent form), with no gender restrictions;
• 3\. Gastrointestinal cancer or gastroesophageal junction adenocarcinoma confirmed by histology and/or cytology, diagnosed as locally advanced according to the 8th edition of the AJCC standards, with a cTNM diagnosis of T3-4aN+M0 and T4aNanyM0 based on ultrasound endoscopy or enhanced CT/MRI scan (and diagnostic laparoscopy if necessary), and agree to receive curative surgical treatment, with the investigator assessing the potential for tumor resectability;
• 4\. Have not previously received systemic treatment for the current disease, including anti-tumor chemotherapy/immunotherapy, etc.;
• 5\. HER2 overexpression confirmed by IHC results from endoscopic biopsy tissue (defined as: IHC 2+, 3+);
• 6\. ECOG score of 0-1;
• 7\. Estimated life expectancy of ≥6 months;
• 8\. Good major organ function:

Exclusion criteria

• 1\. Concurrent malignant disease other than gastric cancer (excluding early-stage tumors that have been radically treated);
• 2\. Tumor lesions with a tendency to bleed (such as active ulcerative tumor lesions with positive fecal occult blood test, history of hematemesis or melena within 2 months before signing the informed consent form, or assessed by the investigator as being at risk of significant gastrointestinal hemorrhage, etc.) or having received blood transfusion treatment within 4 weeks before the study medication; 3. Inability to take oral medication;
• 4\. Currently participating in another interventional clinical study treatment, or having received other investigational drugs or used investigational medical devices within 4 weeks before the first administration of the study medication;
• 5\. Has had systemic treatment required within 2 years before the first administration of the study medication;
• 6\. Known allogeneic organ transplantation (except for corneal transplantation);
• 7\. Known allergy to any medication used in this study;
• 8\. Peripheral neuropathy of grade ≥2;
• 9\. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibodies);
• 10\. Active hepatitis B or C infection;
• 11\. Received live vaccines within 30 days before the first administration (Day 1 of Cycle 1);
• 12\. Pregnant or breastfeeding women;
• 13\. Presence of any severe or uncontrollable systemic disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Ding Y, Qian H, Liu H, Zhang J, Zhang X, Wei J, Chen X, Xu H. DAWN trial: a prospective, multicenter, single-arm phase II study of neoadjuvant disitamab vedotin (RC48) in combination with adebrelimab, apatinib, and S-1 for locally advanced HER2-positive gastric cancer. J Gastrointest Oncol. 2026 Feb 28;17(1):31. doi: 10.21037/jgo-2025-aw-959. Epub 2026 Feb 12. PMID 41816563

Identifiers

NCT: NCT06385873 · 2024-SR-233

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗